To explore the central disturbances resulting from blood pressure changes, spontaneously hypertensive mice (SHM) were compared to normotensive controls for cytochrome oxidase (CO) activity, an index of oxidative capacity in the central nervous system and a marker of long-term regional brain metabolism and neuronal activity. In all brain areas presenting significant enzymatic variations, only increases in CO activity were found in SHM, particularly the central autonomic network. However, only specific regions were affected, namely the insular cortex and the hypothalamic nuclei principally involved in high-order autonomic control. Altered limbic structures included the lateral septum, various hippocampal subregions, as well as prelimbic cortex. CO activity was also elevated in several forebrain regions, including those directly connected to the limbic system, such as the nucleus accumbens, the claustrum, and dorsomedial and reticular thalamic nuclei, as well as subthalamic and ventrolateral thalamic nuclei. In the brainstem, the only regions affected were the locus coeruleus, site of noradrenergic cell bodies, the trigeminal system, and four interconnected regions: the inferior colliculus, the paramedial reticular formation, the medial vestibular, and the cerebellar fastigial nuclei. These data show that specific regions modulating sympathetic nerve discharge are activated in young adult SHM, possibly due to mitochondrial dysfunction and excitotoxicity.